Multiplicative methods, lead optimization

As the drug discovery process proceeds from early lead discovery through lead optimization and toward candidate selection, the level of purity required of each compound increases. Late-stage compounds may be tested in multiple assays, many of which may involve animal models and may be labor-intensive. Even the best solid phase combinatorial synthesis methods cannot assure that... 

The use of molecular biology methods, described in Section 5.3 seems to be especially worthwhile as it offers novel possibilities of optimization on process adjustment. Directed evolution leads to the formation of new biocatalysts with improved characteristics (selectivity, activity, stability, etc.). Incorporation ofnon-proteinogenic amino acids makes it possible to reach beyond the repertoire of building blocks used by nature. The prospect of bioconjugate preparation offers the possibility to form functional clusters of enzymes and to perform multiple synthetic steps in one pot. 

---